Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
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Free will has been the object of debate in the context of addiction given that addiction could compromise an individual's ability to choose freely between alternative courses of action. Proponents of the brain-disease model of addiction have argued that a neuroscience perspective on addiction reduces the attribution of free will because it relocates the cause of the disorder to the brain rather than to the person, thereby diminishing the blame attributed to the person with an addiction. Others have worried that such displacement of free will attribution would make the person with a drug addiction less responsible. Using the paradigmatic literature on the seductive allure of neuroscience explanations, we tested whether neuroscience information diminishes attributions of free will in the context of addiction and whether respondent characteristics influence these attributions and modulate the effect of neuroscience information. We performed a large-scale, web-based experiment with 2,378 German participants to explore how attributions of free will in the context of addiction to either alcohol or cocaine are affected by: (1) a text with a neurobiological explanation of addiction, (2) a neuroimage showing effects of addiction on the brain, and (3) a combination of a text and a neuroimage, in comparison to a control group that received no information. Belief in free will was measured using the FAD-Plus scale and was, subsequent to factor analysis, separated into two factors: responsibility and volition. The investigated respondent characteristics included gender, age, education, self-reported knowledge of neuroscience, substance-use disorder (SUD), and having a friend with SUD. We found that attributions of volition (in the cocaine-subsample) were reduced in the text and neuroimage-treatment compared to the control group. However, respondent characteristics such as education and self-reported knowledge of neuroscience were associated with lower attributions of responsibility for both substances, and education was associated with lower attribution of volition for the alcohol sub-sample. Interaction analyses showed that knowledge of neuroscience was found to generally decrease attribution of responsibility. Further research on attribution of free will should consider the effects of context and respondent characteristics, which appeared surprisingly larger than those induced by experimental treatments.
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PMID:Free Will and the Brain Disease Model of Addiction: The Not So Seductive Allure of Neuroscience and Its Modest Impact on the Attribution of Free Will to People with an Addiction. 2916 57

Tumor cells adapt their metabolism to meet the energetic and anabolic requirements of high proliferation and invasiveness. The metabolic addiction has motivated the development of therapies directed at individual biochemical nodes. However, currently there are few possibilities to target multiple enzymes in tumors simultaneously. Flavin-containing enzymes, ca. 100 proteins in humans, execute key biotransformations in mammalian cells. To expose metabolic addiction, we inactivated a substantial fraction of the flavoproteome in melanoma cells by restricting the supply of the FMN and FAD precursor riboflavin, the vitamin B2. Vitamin B2 deficiency affected stability of many polypeptides and thus resembled the chaperone HSP90 inhibition, the paradigmatic multiple-target approach. In support of this analogy, flavin-depleted proteins increasingly associated with a number of proteostasis network components, as identified by the mass spectrometry analysis of the FAD-free NQO1 aggregates. Proteome-wide analysis of the riboflavin-starved cells revealed a profound inactivation of the mevalonate pathway of cholesterol synthesis, which underlines the manifold cellular vulnerability created by the flavoproteome inactivation. Cell cycle-arrested tumor cells became highly sensitive to alkylating chemotherapy. Our data suggest that the flavoproteome is well suited to design synthetic lethality protocols combining proteostasis manipulation and metabolic reprogramming.
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PMID:Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency. 3289 67